Impact of the type of emulsifier on the physicochemical characteristics of the prepared fish oil-loaded microcapsules

Fish oil microcapsules were successfully prepared from fish oil-in-water emulsions using chitosan as shell material and anionic surfactants sodium dodecyl sulphate (SDS), sodium dodecylbenzenesulfonate (SDBS), sodium cholate (cholate), and sodium deoxycholate (DOC) as emulsifiers. The type of emulsifier influenced the physicochemical characteristics of the prepared microcapsules to different extents. The microcapsules formed with DOC showed the least mean effective diameter (MED) of 500?nm. Emulsion formed with DOC exhibited the smallest MED of 100?nm. The emulsions showed negative zeta potential values which became positive after encapsulation with chitosan. The surfactants showed little influence on thermal stability. Microcapsule suspensions showed creaming over storage. Fish oil at higher loading in SDS microcapsules showed higher primary and secondary oxidation. All microcapsules showed sustained release but the values varied depending upon the surfactants. The emulsion and microcapsules formed with DOC showed better morphology and stability despite its lower loading and encapsulation efficiency.     

胸腺肽乙基纤维素微囊的制备和体外释药研究

 目的为提高胸腺肽的生物利用度，增强疗效，制备了胸腺肽乙基纤维素缓释微囊。方法用液中干燥法制备胸腺肽乙基纤维素微囊，正交设计法筛选其最佳制备工艺，Lowry法测定药物的含量，计算微囊的载药量、包封率及体外释药量。结果微囊粒径范围为30-80ym，平均粒径为52.64 tim，平均含药量为20.420h，平均包封率为81.64%，其体外释药符合Higuchi方程Q=5.15387+35. 350 59t1/2(r=0.997,n=9)，f1／2-80min，稳定性考察实验结果表明其稳定性较好。结论本法制备的胸腺肽乙基纤维素微囊粒径分布集中，体外释药有明显的缓释作用，具有良好应用前景。     

Control of mosquito larvae by encapsulated pathogen Bacillus thuringiensis var. israelensis

Abstract

Bacillus thuringiensis var. israelensis (B.t.i.) containing alginate microcapsules were prepared in order to maintain durable formulations which could resist several effects causing reduced efficiency during applications. B.t.i. spores were harvested through NYSM agar plates and encapsulated in Ca-alginate (0.5–2.0% w/v) gels without any significant loss of sporal or larvicidal activity. The effect of acidic pH on the larvicidal toxin was tested using Culex sp. larvae in the laboratory. The alginate microcapsules pretreated with saturated KH₂PO₄ solution gave larvicidal activity after 24–48h, by bioassay. Suspension and encapsulated forms of the pathogenic bacterium were exposed to pH variations (3.4–10.0), UV light and high temperature (50°C). Durability to Pb ^{+ +}, Cu⁺⁺, Fe^{+ +} compounds and phenol was also examined. As the alginate content increased, stability of B.t.i. drastically increased against the tested effects, but to obtain useful releasing microcapsules, 14–1.5% w/v alginate concentrations were found to be optimum.     

Influence of pH adjustment on microcapsules obtained from complex coacervation of gelatin and acacia

Abstract

The coacervation behaviour of commercial grade gelatin and acacia mixtures was studied with five different acids to adjust the coacervation pH, i.e. HCI, HNO₃, H₂SO₄, acetic acid, and citric acid. The electrical equivalence pH value (EEP) of the polymer mixture was determined by means of a streaming current detector (SCD). With all acids-except H₂SO₄-maximum coacervate yield was observed at the EEP. Using H₂SO₄ the EEP was found at a lower pH value than compared with the point of maximum coacervate yield. The quantity of coacervate at the EEP was significantly reduced in the presence of H₂SO₄ whereas with all other acids, almost no differences were found. The dependence of the coacervate volume on the added amount of acid did not change in parallel to the dry coacervate yield and there was no coincidence of the maximum coacervate volume and the EEP. The barrier properties of the capsule shells of corresponding microcapsules using indomethacin as a model drug were examined by dissolution studies. Indomethacin microcapsules showed the slowest release rate when the coacervation pH was adjusted to the EEP and not to the pH of maximum coacervate yield. As expected from the coacervation behaviour, dissolution profiles of the microcapsules were quite similar even when different acids were used for pH adjustment.     

莲子心微囊中总生物碱的含量测定

目的建立莲子心微囊中总生物碱的含量测定方法。方法紫外分光光度法,以莲心碱为对照品,测定波长为282nm。结果莲子心微囊中总生物碱浓度在5.32~58.52μg/m l范围内线性关系良好,其线性回归方程为:A=0.017 573C-0.046 418,r=0.999 9(n=5),加样回收率为99.55%。结论该测定方法稳定、快速、简便,测定结果良好,可以有效控制莲子心微囊的质量。     

蛇床子素缓释微囊的制备及体外释药

目的:制备蛇床子素缓释微囊并考察其体外释放规律。方法:以明胶、阿拉伯胶为囊材,采用复凝聚法制备微囊,采用紫外分光光度法测含量,均匀设计优化制备工艺。分别以150 mL人工胃液与磷酸盐缓冲液(pH 6.8)为溶出介质,温度(37±0.5)℃,转速100 r·min-1,测定其体外释放度。结果:最佳制备工艺为囊心囊材质量比1∶1.5,温度60℃,戊二醛用量0.8∶120(戊二醛用量/系统体积),制备的微囊圆整光滑,粒径均匀,平均粒径(51.6±4)μm,包封率85.0%,载药量47.2%,体外缓释时间为6 h,其释药特征符合一级动力学过程。结论:蛇床子素微囊制备工艺简单,成囊性和重复性好,微囊具有明显的缓释效果。     

喷雾干燥法制备丹酚酸壳聚糖微囊

目的以壳聚糖为载体制备丹酚酸微囊,并对其体外释药模式进行研究。方法以收率和载药量为指标,考察处方及工艺因素对微囊的影响,并对处方和工艺进行优化。结果壳聚糖质量浓度1.5%,丹酚酸与壳聚糖的质量比1∶3,进风温度190℃,蠕动泵速度300mL.h-1,所制得的微囊表面圆整,载药量为25.99%,收率为51.88%,包封率为86.21%,平均粒径为105.6nm。体外具有一定的缓释特性,在0～240min内拟合一级释药模型方程ln(1-Q)=-0.236 9 t+4.591 7,r=0.920 3。结论采用喷雾干燥法制得的丹酚酸微囊,收率和载药量较高,制备工艺简单,可望成为实现中药微球工业化的有效方法。     

三七总皂苷肠溶微囊的药代动力学及体内外相关性

目的:考察三七总皂苷(panax notoginseng saponins,PNS)肠溶微囊在Beagle犬体内的释药行为及其体内外相关性研究。方法:采用双周期交叉试验设计,6只健康Beagle犬口服市售血栓通胶囊或自制PNS肠溶微囊(胶囊型)后,用HPLC法测定血药浓度,计算两制剂的药代动力学参数,进行生物利用度比较,并对体外累积释放度和体内累积吸收百分率进行线性回归。结果:自制PNS肠溶微囊对市售血栓通胶囊的相对生物利用度为三七皂苷R1(R1)313.63%,人参皂苷Rb1(Rb1)314.35%,人参皂苷Rg1(Rg1)202.03%,上述3成分在体内的平均滞留时间均延长,R1,Rb1和Rg1的体内外相关系数分别为0.866 4,0.958 0和0.719 2。结论:自制PNS肠溶微囊与市售血栓通胶囊相比生物利用度更高,Rb1体内外相关性较好,可用一定的体外释放条件进行体内行为的预测,R1和Rg1体内外相关性较差。     

Investigation of alternative compounds to poly(E-MA) as a polymeric surfactant for preparation of microcapsules by phase separation method

Various water-soluble polymers were used to examine an alternative emulsifier for poly(ethylene-alt-maleic anhydride), used in the preparation of crosslinked polyurea microcapsules. Microcapsules were successfully prepared by using the water-soluble polymers with large molecular weight alternating copolymers, namely poly(olefin-maleic anhydride), poly(olefin-maleic acid), and poly(acrylic acid). On the other hand, no microcapsule resulted from olefin-maleic acid with small molecular weight alternating copolymers. From these results, the following guidelines were obtained for the selection of polymeric surfactants suitable for crosslinked polyurea microcapsule. A polymeric surfactant must have maleic acid or a carboxyl group in order to form a crosslinked polyurea microcapsule membrane. Furthermore, to form a stronger capsule membrane it is desirable to have a maleic anhydride group. It is also important for membrane formation that the polymeric surfactant has a suitable molecular weight.     

Plasmodium falciparum synthetic LbL microparticle vaccine elicits protective neutralizing antibody and parasite-specific cellular immune responses

Epitopes of the circumsporozoite (CS) protein of Plasmodium falciparum, the most pathogenic species of the malaria parasite, have been shown to elicit protective immunity in experimental animals and human volunteers. The mechanisms of immunity include parasite-neutralizing antibodies that can inhibit parasite motility in the skin at the site of infection and in the bloodstream during transit to the hepatocyte host cell and also block interaction with host cell receptors on hepatocytes. In addition, specific CD4+ and CD8+ cellular mechanisms target the intracellular hepatic forms, thus preventing release of erythrocytic stage parasites from the infected hepatocyte and the ensuing blood stage cycle responsible for clinical disease. An innovative method for producing particle vaccines, layer-by-layer (LbL) fabrication of polypeptide films on solid CaCO₃ cores, was used to produce synthetic malaria vaccines containing a tri-epitope CS peptide T1BT* comprising the antibody epitope of the CS repeat region (B) and two T-cell epitopes, the highly conserved T1 epitope and the universal epitope T*. Mice immunized with microparticles loaded with T1BT* peptide developed parasite-neutralizing antibodies and malaria-specific T-cell responses including cytotoxic effector T-cells. Protection from liver stage infection following challenge with live sporozoites from infected mosquitoes correlated with neutralizing antibody levels. Although some immunized mice with low or undetectable neutralizing antibodies were also protected, depletion of T-cells prior to challenge resulted in the majority of mice remaining resistant to challenge. In addition, mice immunized with microparticles bearing only T-cell epitopes were not protected, demonstrating that cellular immunity alone was not sufficient for protective immunity. Although the microparticles without adjuvant were immunogenic and protective, a simple modification with the lipopeptide TLR2 agonist Pam₃Cys increased the potency and efficacy of the LbL vaccine candidate. This study demonstrates the potential of LbL particles as promising malaria vaccine candidates using the T1BT* epitopes from the P. falciparum CS protein.